Proof of concept nanotechnological approach to in vitro targeting of malignant melanoma for enhanced immune checkpoint inhibition

by Selleckchem | Jul 04 2023

Immunotherapies, including immune checkpoint inhibitors, have limitations in their effective treatment of malignancies. The immunosuppressive environment associated with the tumor microenvironment may prevent the achievement of optimal outcomes for immune checkpoint inhibitors alone, and nanotechnology-based platforms for delivery of immunotherapeutic agents are increasingly being investigated for their potential to improve the efficacy of immune checkpoint blockade therapy. In this manuscript, nanoparticles were designed with appropriate size and surface characteristics to enhance their retention of payload so that they can transmit their loaded drugs to the tumor. We aimed to enhance immune cell stimulation by a small molecule inhibitor of PD-1/PD-L1 (BMS202) using nanodiamonds (ND). Melanoma cells with different disease stages were exposed to bare NDs, BMS202-NDs or BMS202 alone for 6 h. Following this, melanoma cells were co-cultured with freshly isolated human peripheral blood mononuclear cells (hPBMCs). The effects of this treatment combination on melanoma cells were examined on several biological parameters including cell viability, cell membrane damage, lysosomal mass/pH changes and expression of γHA2X, and caspase 3. Exposing melanoma cells to BMS202-NDs led to a stronger than normal interaction between the hPBMCs and the melanoma cells, with significant anti-proliferative effects. We therefore conclude that melanoma therapy has the potential to be enhanced by non-classical T-cell Immune responses via immune checkpoint inhibitors delivered by nanodiamonds-based nanoparticles.

Comments:

The manuscript describes a study that explores the use of nanotechnology-based platforms to improve the efficacy of immune checkpoint inhibitors in treating malignancies. The authors designed nanoparticles with specific size and surface characteristics to enhance their ability to carry therapeutic agents to the tumor site. In this case, they aimed to enhance immune cell stimulation using a small molecule inhibitor of the PD-1/PD-L1 pathway called BMS202, delivered using nanodiamonds (ND).

To evaluate the effects of this treatment combination, the authors exposed melanoma cells of different disease stages to bare NDs, BMS202-NDs, or BMS202 alone for a period of 6 hours. Afterward, the melanoma cells were co-cultured with freshly isolated human peripheral blood mononuclear cells (hPBMCs). Several biological parameters were examined to assess the effects of the treatment, including cell viability, cell membrane damage, lysosomal mass/pH changes, and the expression of γHA2X and caspase 3, which are markers of cellular damage and apoptosis.

The results demonstrated that exposing melanoma cells to BMS202-NDs resulted in a stronger interaction between hPBMCs and melanoma cells compared to the other treatments. This enhanced interaction led to significant anti-proliferative effects on the melanoma cells. The findings suggest that delivering immune checkpoint inhibitors using nanodiamond-based nanoparticles can enhance melanoma therapy by promoting non-classical T-cell immune responses.

In summary, the study highlights the potential of using nanotechnology-based platforms for delivering immunotherapeutic agents, specifically immune checkpoint inhibitors, to overcome the limitations associated with the immunosuppressive tumor microenvironment. By enhancing immune cell stimulation and promoting stronger interactions between immune cells and cancer cells, these nanodiamond-based nanoparticles could improve the efficacy of melanoma therapy. Further research in this area may help refine and develop this approach for future clinical applications.